In September, 2006, the National Eye Institute funded the Comparison of AMD Treatments Trials (CATT). This 4-arm, 1200 patient study was designed to determine the relative efficacy of Lucentis and Avastin and to evaluate their optimal dosing frequencies. Patient enrollment was planned to have begun in early 2007, however, regulatory hurdles including obtaining reimbursement for these agents by CMS extended the period of the trial beyond its current funding. In addition, it has become clear that the long term visual outcomes including safety and efficacy beyond two years are completely unknown. Given that Lucentis and Avastin are now the basis for virtually all AMD treatment worldwide and that these patients require continued dosing for many years beyond the previous periods of study, it is clear that the long term effects of these drugs must be understood. In this application, support for two initiatives is requested: Specific Aim #1: To complete the CATT: Lucentis-Avastin randomized clinical trial. The current period of funding ends August 2010. The last patient enrolled will complete their two year period of treatment in December 2011. Funding is requested to insure all patients are supported through completion of the first phase of the CATT study. Specific Aim #2: To conduct an observational Follow-up Study to investigate the course of visual acuity and the ocular and systemic safety of long-term treatment with Lucentis or Avastin. Patients who complete two years of treatment in the randomized clinical trial will be followed in an observational study for an additional three years. RELEVANCE (See instructions): The development of Lucentis and Avastin represents a major therapeutic improvement over previous therapies for AMD and has profoundly altered expectations regarding the extent of visual loss that can be prevented or reversed. No single study has compared the safety and efficacy of these two agents head to head or looked at comparative outcomes of these agents using monthly or as needed dosing regimens.